IMMUNE MODULATORY EFFECT OF HYPERTHERMIA DURING TREATMENT OF RECURRENT, METASTATIC OR LOCALLY ADVANCED SOLID ORGAN MALIGNANCIES

Received 2023-05-11; Accepted 2024-01-09; Published 2024-08-01

Abstract

Background: The use of hyperthermia as an adjunct to improve conventional therapies in multimodal cancer treatment is supported by an increasing body of research. The underlying biological contribution of hyperthermia in modulating the cells of the immune system has been a growing area of interest. This study aims to evaluate the immune modulatory effect of locoregional hyperthermia given with standard of care treatment for patients with recurrent or metastatic solid malignancies. Secondary endpoints were tolerability, change in pain score and quality of life, and tumour control rate.

Methods: A single-centre prospective study, conducted from December 2019 to December 2021 at the University of Malaya Medical Centre, recruited 30 patients with solid organ malignancy at baseline. Alongside standard cancer treatment, patients also received hyperthermia treatment for 2 hours, two or three times a week for up to 16-weeks using REMISSION1ºC hyperthermia-induction device. Flow cytometry for lymphocyte enumeration and immunophenotyping was done on blood samples collected from patients at 4 different time points (Baseline, week 1 post hyperthermia, week 1 post standard therapy, week 4.

Results: In the analysis of lymphocyte subsets, an increase in CD8+ central memory T cells between baseline and week 1 post hyperthermia (Mean: Baseline 3.854, Week 1A 5.818; P = 0.013) was noted. An increase of CD4+ effector memory T cells between baseline and week 4 post hyperthermia in conjunction with standard therapy (Mean: Baseline 33.60, Week 4 39.34; P = 0.022) was recorded. There was also a marked increase in the percentage of CD8+ T cell expressing checkpoint inhibitory marker PD-1 post week 1 hyperthermia treatment (Mean: Baseline 7.439, week 1A 9.757; P = 0.048) as well as post standard treatment (Mean: Baseline 7.439, Week 1B 9.222; P = 0.033) from baseline.

Conclusion: Hyperthermia produced significant effects on the immune cell profiles of cancer patients on treatment. The subset of CD4 effector memory T cells increased significantly, although there was also sign of increased T cells exhaustion. These findings serve as a stepping stone for further research in exploring the mechanisms of hyperthermia in immune modulation and also its translation into clinical practice.